title: COX-2 is not required for the development of murine chronic pancreatitis.
abstract: Chronic pancreatitis is a severe inflammation of the pancreas associated with destruction of the parenchyma, fibrosis, and persistent abdominal pain. Cyclooxygenase-2 (COX-2) and COX-2-derived prostaglandins, key mediators of the inflammatory response, are elevated in patients with chronic pancreatitis. Previous studies investigated COX-2 as a therapeutic target. These reports showed a reduced pathology in COX-2-deficient mice with a better outcome. Here we compared the role of COX-2 in acute and chronic pancreatic inflammation using the same COX-2(-/-) mouse model of cerulein-induced pancreatitis. In a setting of acute pancreatitis, juvenile COX-2(-/-) mice exhibited a reduced histopathological score compared with wild-type littermates; on the contrary, adult mice did not show any difference in the development of the disease. Similarly, in a setting of chronic pancreatitis induced over a period of 4 wk, adult mice of the two strains showed comparable histological score and collagen deposition. However, the abundance of mRNAs coding for profibrotic genes, such as collagen, α-smooth muscle actin, and transforming growth factor-β was consistently lower in COX-2(-/-) mice. In addition, comparable histological scores and collagen deposition were observed in wild-type mice treated with a COX-2 inhibitor. We conclude that, in contrast to what was observed in the rat pancreatitis models, COX-2 has a limited and age-dependent effect on inflammatory processes in the mouse pancreas. These results suggest that COX-2 modulates the inflammatory process during the development of pancreatitis in a species-specific manner. Thus the pathophysiological roles of COX-2 and its therapeutic implications in patients with pancreatitis should be reexamined.
authors.affiliation: Swiss HPB Center, Pancreatitis Research Laboratory, Department of Visceral and Transplantation Surgery, University Hospital, Zurich, Switzerland.
authors.forename: Alberto
authors.initials: A
authors.lastname: Silva
authors.forename: Achim
authors.initials: A
authors.lastname: Weber
authors.forename: Martha
authors.initials: M
authors.lastname: Bain
authors.forename: Theresia
authors.initials: T
authors.lastname: Reding
authors.forename: Mathias
authors.initials: M
authors.lastname: Heikenwalder
authors.forename: Sabrina
authors.initials: S
authors.lastname: Sonda
authors.forename: Rolf
authors.initials: R
authors.lastname: Graf
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D002108:Ceruletide; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007783:Lactones / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D050500:Pancreatitis, Chronic / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D013045:Species Specificity; D013450:Sulfones / Q000494:pharmacology; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D013450:Sulfones; D016212:Transforming Growth Factor beta; C116926:rofecoxib; D002108:Ceruletide; D003094:Collagen; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2